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Colchicine inhibits NLRP3. 120 / 120
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"Colchicine acts by impairing leukocyte locomotion and interfering with the assembly of multiple components that comprise inflammasomes.49 There are studies also suggesting that colchicine may prevent NLRP3 inflammasome activation.50The effect of colchicine on cardiovascular events was first investigated in a randomized, open-label study, the Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease (LoDoCo) trial, that tested whether colchicine 0.5 mg/day prevented recurrent cardiovascular events."
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"Moreover, colchicine downregulates NLRP3 inflammasome by antagonizing caspase-1 activity and potential triggering factors (e.g., P2X2 and P2X7 channels and Reactive Oxygen Species) (104)."
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"It was previously demonstrated that colchicine suppressed the activity of NLRP3 inflammasome (31)."
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"Therefore, it is plausible to think that colchicine inhibits IL-1β production by suppressing the NLRP3 activity to ameliorate the symptoms of PFAPA."
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"Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients."
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"Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19."
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"By measuring the serum concentration of Casp1p20 and IL-18, we found that colchicine inhibited the activation of the NLRP3 inflammasome."
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"On the other hand, the use of colchicine that can inhibit NLRP3, had no clinical benefit in patients with COVID-19 (17)."
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"We did not evaluate the function of NLRP3 inflammasome ex vivo nor whether colchicine would reduce the activation of NLRP3 inflammasome in vitro."
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"Colchicine suppresses NLRP3 inflammasome, by disrupting the microtubule‐dependent transport of mitochondria to the endoplasmatic reticulum, whose assembly with its adaptor and NLRP3 is required to be activated with inflammasomes (Lopes et al., 2021)."
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"However, colchicine is a microtubule inhibitor and potentially inhibits the NLRP3 inflammasome at various points [2, 19] and has been shown to reduce pro-inflammatory cytokines including interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6), as well as the inflammatory marker C-reactive protein (CRP) in a variety of experimental models and clinical settings [2, 19]."
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"Considering that colchicine has shown to inhibit NLRP3 inflammasome and neutrophil activation, it has been considered a valid candidate as potential treatment for COVID-19 ."
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"As an anti-inflammatory compound, colchicine can inhibit the production of IL-1β and the activation of the NLRP3 inflammasome [18], thereby attracting considerable interest within the scientific community."
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"Role of colchicine to reduce NLRP3 marker in STEMI patients undergo primary PCI: A randomised controlled clinical trial."
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"Martinon et al. initially demonstrated that colchicine could inhibit the activation of the NLRP3 inflammasome in cultured monocytes [130]."
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"NSAIDs inhibit production of cyclo-oxygenase; glucocorticoids inhibit transcription of inflammatory genes, and colchicine blocks activity of the NLRP3 inflammasome [26]."
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"Additionally, several NLRP3 inflammasome inhibitors such as colchicine, OLT1177 and MCC950 have also been identified to inhibit the activity of ATPase and prevent the assembly and activation of NLRP3 inflammasome."
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"In contrast, colchicine attenuated the activation of NLRP3, and the combination of SIRT2 with NLRP3 was remarkably elevated (Figure 5A)."
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"Furthermore, colchicine also inhibits NLRP3 inflammasome polymerization (Martinon et al., 2009; Martínez et al., 2018)."
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"36 , 37 Low‐dose colchicine alters the conformation of tubulin and interferes with the stability of microtubules, preventing the activation of the NLRP3 inflammasome."
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"Colchicine, at the molecular level, inhibits NLRP3 inflammasome, in addition to the inhibition of nuclear factor kappa B (Zhang et al., 2022)."
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"Conversely, colchicine, which inhibits the NLRP3 inflammasome, was effective in reducing MACE."
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"Colchicine can block NLRP3 and thus IL-1β production [23]."
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"Colchicine is another therapeutically utilized drug that inhibits NLRP3 and has an excellent safety profile in humans [ 51 ]."
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"The seminal LoDoCo (Low Dose Colchicine trial) and COLCOT (Colchicine Cardiovascular Outcomes Trial) trials found that low-dose colchicine significantly reduces the risk of cardiovascular death not only in the setting of stable coronary artery disease (CAD) but also in acute coronary syndromes [4,5]; indeed, colchicine suppresses the activation of inflammasome NLRP3 in neutrophils and macrophages by inhibiting tubulin polymerization and microtubule generation."
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"Colchicine, a well-known anti-inflammatory drug, has been shown to inhibit the NLRP3 inflammasome in micromolar concentrations potently."
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"However, it is unclear whether colchicine could suppress the activation of NLRP3 inflammasome and cell pyroptosis induced by CC in the progression of AS, and direct evidence for AMPK/SIRT1 activation in antagonizing inflammasome and pyroptosis is still lacking.In this study, we discovered that colchicine could upregulate the expression and activity of various antioxidant enzymes, inhibit ROS production and NLRP3 inflammasome activation, and antagonize endothelial cell pyroptosis which was induced by CC via activating the AMPK-SIRT1 pathway."
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"Colchicine supplementation could significantly protect SIRT2 from inactivation and suppress the aberrant activation of the NLRP3 inflammasome."
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"Martinon F. et al. proved that colchicine can inhibit the activation of the NLRP3 inflammasome in cultured monocytes.34 Current studies have shown that the mechanism of colchicine on the NLRP3 inflammasome can be summarized into the following three types.3.2.1 Colchicine can restrict P2X7 receptor."
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"Treatment with colchicine successfully attenuates NLRP3 inflammasome activity, improves cardiac function, and prolongs survival after MI 66.Besides the inhibitors that directly affect NLRP3, there are agents that can suppress the activity of NLRP3 indirectly."
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"A small, randomized trial of patients with COVID-19 demonstrated the ability of colchicine, which indirectly inhibits the NLRP3 inflammasome, to reduce the requirement of oxygen [186], though current NIH guidelines do not recommend colchicine for the treatment of COVID-19 [187]."
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"Conversely, colchicine treatment significantly blocked NLRP3 signal activity; the expression levels of NLRP3 and ASC-1 were nearly half compared with the CC group (Figures 2(b) and 2(c))."
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"At the molecular level, colchicine blocks the assembly of NLRP3 via preventing microtubule polymerization and inhibits the production of IL-8 and IL-1β, thereby inhibiting the process of inflammation."
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"Nevertheless, emerging evidence suggests that colchicine may exert effects on other key aspects of the inflammatory process, potentially influencing monocytes/macrophages, neutrophils, and platelets (Figure 1).3.1 Colchicine inhibition of the NLRP3 inflammasome."
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"In addition, colchicine suppresses the assembly and activation of the NLRP3 inflammasome, which leads to a decrease in inflammatory markers (IL-1β, IL-18, IL-6, TNF-α, and C-reactive protein), inhibition of foam cell formation, and atherosclerotic plaque stabilization [20,21]."
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"Therefore, it is plausible to suppose that colchicine may upregulate the expression and activity of various antioxidant enzymes and reduce the production of ROS via activating the AMPK-SIRT1 pathway, thus restraining the activation of NLRP3 inflammasome and endothelial cell pyroptosis induced by CC."
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"Colchicine, a very cheap drug, can effectively block NLRP3 inflammasomes and reduce inflammation."
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"Finally, colchicine can also inhibit the activation of the NLRP3 inflammasome and reducing the pro‐inflammatory cytokines production."
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"More recently, colchicine has been shown to decrease cytokine production by inhibiting activation of the NLRP3 inflammasome (figure 5)."
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"Colchicine can inhibit the activation of NLRP3 in the inflammasome and also directly inhibit the synthesis of TNF-α and IL-6 [156]."
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"Results from CANTOS trial suggest that colchicine, which can also inhibit NLRP3 inflammasome-IL-1β pathway as an anti-inflammatory drug, is supposed to similarly reduce CV risk in CAD patients."
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"Colchicine, a widely used gout medication with anti-inflammatory properties, disrupts the NLRP3 inflammasome pathway through a multi-faceted mechanism."
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"Colchicine inhibits neutrophil migration and the NLRP3 inflammasome."
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"Colchicine downregulates multiple inflammatory pathways including the NLRP3 inflammasome implicated in acute lung injury [17,38] and modulates innate immunity [36,[39], [40], [41], [42]]."
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"Studies have shown that colchicine inhibits the activity of the NLRP3 (NOD-like receptor family Pyrin Domain-Containing 3) inflammasome, leading to the decreased secretion of pro-inflammatory cytokine[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"According to recent research, colchicine can inhibit NLRP3 activation in the following ways."
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"Apart from its effect on neutrophil activity, colchicine can indirectly block the NLRP3 inflammasome [20, 21], a macromolecular complex that senses danger and triggers a local or systemic inflammatory response by releasing pro-inflammatory cytokines, such as IL-1β [22]."
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"However, a high dose of colchicine is required to inhibit the NLRP3 inflammasome, and the use of this treatment in patients with renal insufficiency may be limited by the risk of colchicine toxicity because of the increased half-life of the drug [249, 250] ."
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"Colchicine can suppress the uptake of CHCs by endothelial cells, and attenuate the occurrence of NLRP3 inflammasome and pyroptosis by inhibiting mtROS production and oxidative stress through the AMP-dependent kinase (AMPK) / Sirtuin1 pathway 38."
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"In recent years, colchicine was found to inhibit NLRP3 inflammasome, although the exact mechanism of action is not fully understood yet."
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"Indeed, colchicine is known to block the NLRP3 inflammasome and has many advantages, such as a limited immunosuppression, oral administration, and few side effects."
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"Colchicine, for example, disrupts different cellular processes including the NLRP3 inflammasome as well as processes leading to cytokine storm and was therefore investigated as a therapeutic option against COVID-19 [33], [34]."
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"Colchicine at a dose of 0.5 mg once daily reduces inflammasome (NLRP3) activation and neutrophil degranulation (5, 6)."
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"As an anti-inflammatory drug, colchicine inhibited the activation of NLRP3 inflammasome as well as pyroptosis [34,35]."
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"In a mouse model of AMI, treatment with oral colchicine (0.1 mg/kg/d for 7 consecutive days) significantly reduced activation of the NLRP3 inflammasome and expression of downstream pyroptosis-related proteins of NLRP3 after 24 h."
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"Recent studies have shown that colchicine inhibits the NLRP3 inflammasome by reducing pore formation induced by P X (36), inhibiting caspase-1 activation (37), and suppressing microtubule synthesis (38)."
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"Given the important role of colchicine in inhibiting the activation of NLRP3 inflammasome, it may have the potential to treat DCM."
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"Moreover, colchicine inhibits the NLRP-3 inflammasome by reducing cleavage of prointerleukin-1β to active interleukin-1β [13,14] ."
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"This hypothesis is supported in recent clinical studies suggesting that non-selective NLRP3 inhibition by colchicine in COVID-19 patients with FMF may influence the clinical presentation of the infection."
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"Only the old and aspecific anti-inflammatory drug colchicine, which inhibits the assembly of the NLRP3 inflammasome, was recently evaluated in a clinical trial."
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"In vitro, at micromolar concentrations, colchicine inhibits MSU crystal activation of the NLRP3 inflammasome, blocks the release of IL-1β, and suppresses the expression of genes involved in cell regul[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"9 NLRP3 inflammasome can be inhibited by clinically supratherapeutic levels of colchicine."
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"Meanwhile, colchicine can prevent NSAID enteropathy by inhibiting the activation of NLRP3 inflammasome (Otani et al., 2016)."
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"Colchicine, an alkaloid derivative of the Colchicum genus plants, inhibits IL-1β and IL-18 by interacting with the inflammasome Nod-like receptor protein 3 inflammasome protein complex 1 (NLRP-3), for which it is hypothesized that it could be useful in severe Covid-19 Pneumonia [24]."
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"Importantly, the anti-inflammatory drug colchicine, which has demonstrated beneficial effects on MACE after MI [310] and in patients with chronic coronary disease [311], inhibits NLR family pyrin domain containing 3 (NLRP3) inflammasome and reduces EV-associated NLRP3 protein levels [312]."
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"Thus, colchicine inhibits P2X7R, P2X2R, and consequently NLRP3 inflammasome which ultimately attenuates cytokine storm."
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"Therefore, we considered that higher concentrations of nigericin might activate the inflammasome in the absence of the speck, but whether colchicine blockade of NLRP3:ASC speck assembly is overcome under these conditions is untested."
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"Colchicine blocks the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18."
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"Colchicine inhibits the activation of NLRP3 inflammasome and thus reduces the production of interleukin (IL)-1β and IL-18 mediated by it (51, 52) since neutrophil enzymes activate IL-1β and IL-18 extracellularly, and colchicine also inhibits the reduction of the release of neutrophil granulocyte enzymes associated with thrombosis, which is one of its potential anti-inflammatory mechanisms (53, 54)."
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"Several studies indicate that colchicine inhibits the activation of NLRP3 inflammasome, leading to a potent reduction of IL-1β production, which, in turn, prevents the cytokine storm."
| PMC
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"In recent studies, colchicine has been shown to inhibit the stimulation of the NLRP3 inflammasome, which can hinder the presentation of irritant agents and block microtubule assembly (33, 87)."
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"NLRP3 inflammasome inhibitors such as tranilast, tetracycline, resveratrol, nicardipine, erythropoietin and colchicine are under clinical trials for management of COVID-19 [16]."
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"Colchicine can inhibit the activation of NLRP3 inflammasome by inhibiting the P2X7 receptor and blocking potassium efflux."
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"Colchicine has been found to inhibit the inflammasome activation of NLRP3 (NLR Family Pyrin Domain Containing 3) and pyrin domain and is being investigated for its use in COVID-19 management (PMID: [224], PMID: 32732245, PMID: 32472681)."
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"Moreover, colchicine can also inhibit microtubule synthesis, promote microtubule degradation, and inhibit the assembly of NLRP3 inflammasome (162)."
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"38,39 Colchicine, an inhibitor of tubulin polymerization, suppresses NLRP3 inflammasome-dependent production of IL-1β."
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"Although the mechanism of the benefit of colchicine was not investigated in this trial, colchicine has been shown to acutely lower the local production of NLRP3 inflammasome-related cytokines, IL-1β, IL-18, and IL-6, in the coronary vascular bed of patients with CAD [168]."
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"60 In addition to interfering with monocyte and neutrophil chemotaxis, colchicine also indirectly inhibits NLRP3 activation.61 Indeed, colchicine has been tested in multiple RCTs for COVID-19.47–52 The RECOVERY (Randomised Evaluation of COVID-19 Therapy) arm with colchicine was stopped due to futility.49 Like the other NLRP3-targeted drugs mentioned above, colchicine seemed to have minimal effects in community-treated patients without a mandatory diagnostic test but led to a lower rate of the composite of death or admission to the hospital among those with PCR-confirmed COVID-19."
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"In addition, previous studies have demonstrated that colchicine can reduce NALP3 inflammasome-driven caspase-1 activation by preventing microtubule assembly and MSU delivery (39)."
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"In addition to the indirect action on chemotaxis, motility, and stimulation of leukocytes, colchicine has been demonstrated to inhibit the NLRP3 inflammasome, thereby suppressing caspase-1 activation in gout [108]."
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"Colchicine has been demonstrated to inhibit the NLRP3 inflammasome and suppress caspase-1 activation in gout [25]."
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"In addition to the indirect action on chemotaxis, motility, and stimulation of leukocytes, colchicine has been demonstrated to inhibit the NLRP3 inflammasome, thereby suppressing caspase-1 activation (32)."
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"Several studies indicate that colchicine inhibits the activation of NLRP3 inflammasome leading to a potent reduction of IL-1β production, which will, in turn, prevent the cytokine storm."
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"Colchicine inhibits the NLRP3 inflammasome activity as part of its microtubule-disassembling properties [ 34 ]."
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"For the first time, the authors also showed that colchicine, applied in the early phase of CVB3 infection (after 24 h), decreased the NLRP3 inflammasome activity in cardiac and splenic macrophages (F4[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In the present study, we demonstrated a significantly elevated level of several components (NF-κB p65, NLRP3, caspase-1, IL-1β and IL-18) in NF-κB/NLRP3 pathways in atherosclerotic plaques, while systemic administration of free colchicine and VHPK-PLGA@COL into AS mice significantly downregulated the expression level of these inflammatory components, whereby the downregulation of NF-κB may play a central role in colchicine-mediated inhibition of NLRP3 inflammasome pathways."
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"Colchicine, a microtubule polymerization inhibitor, has been identified with the ability to inhibit NLRP3 inflammasome and investigated in clinical trials for COVID-19."
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"Colchicine improved survival and preserved left ventricular systolic function in mice at 4 weeks after permanent coronary artery ligation, and reduced myocardial mRNA of NLRP3 inflammasome components [207]."
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"However, the use of colchicine therapy, which requires high concentrations to inhibit the NLRP3 inflammasome, may be limited in patients with kidney dysfunction due to increased drug half-life and the risk of colchicine toxicity [244]."
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"A proteomic substudy of LoDoCo2 confirmed that colchicine attenuates the NLRP3 inflammasome pathway, including IL-18, IL-1 receptor antagonist, and IL-6, in patients with chronic artery disease."
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"In a murine myocardial infarct model, with doses comparable to those employed in humans (0.1 mg/kg), colchicine attenuated the activation of NLRP3 inflammasome constituents over and above the decrement in inflammatory mediators [9,91,92]."
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"Pretreatment with colchicine can reduce myocardial pyroptosis by inhibiting the activation of NLRP3 inflammasome, thus reducing the damage of cardiomyocytes and improving the cardiac function of rats."
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"We found that colchicine pretreatment inhibited the activation of NLRP3 inflammasome and reduced myocardial pyroptosis, thus reducing myocardial injury and improving cardiac dysfunction in rats with CME."
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"In addition, in a clinical cohort study, colchicine decreased stroke outcomes by inhibiting NLRP3 activation."
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"In recent years, colchicine has been shown to inhibit the NLRP3 inflammasome in various ways, thereby potentially benefiting patients with CAD."
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"Recent studies have shown that colchicine, one of the oldest anti-inflammatory drugs, can reduce the risk of hospitalization and mortality among COVID-19 patients by targeting the NLRP3 inflammasome to alleviate hyperinflammation.34,81 Interestingly, although AC was effective in reducing body weight loss and ameliorating lung injury in SARS-CoV-2-infected hamsters, it did not significantly reduce virus replication."
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"In addition, colchicine decreases IL-1β and IL-18 by inhibiting the NLRP3 inflammasome [149]."
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"Finally, and based on studies carried out in microcrystalline arthropathies, it has been shown that colchicine suppresses the activation of the inflammasome (NLRP3) induced by calcium pyrophosphate and monosodium urate crystals."
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"al. observed that the levels of NLRP3, caspase-1 and IL-1β significantly increase in the small intestine upon indomethacin induced small intestine injury, and colchicine could inhibit the activation of NLRP3 inflammasome [299]."
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"This was further reinforced by AF recurrence being able to be lowered by colchicine administration, which inhibits the NLR family pyrin domain containing 3 inflammasome, in a randomized trial by Deftereos et al.17 Likewise, higher levels of fibrosis markers have also been linked with AF recurrence, such as transforming growth factor-β1 and galectin-3, which is secreted by activated macrophages, serving as a possible link between increased inflammation, fibrosis, and AF recurrence."
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"Colchicine can also inhibit NLRP3 inflammasome signaling by irreversibly inhibiting tubulin polymerization and microtubules (112)."
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"In summary, colchicine inhibits the activation of NLRP3 inflammasome through the AMPK/SIRT1/NLRP3 signaling pathway, and inhibits CME-mediated myocardial pyroptosis, thereby alleviating myocardial injury and improving cardiac function."
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"More recently, it has been demonstrated that colchicine also reduces NALP3 inflammasome-driven caspase-1 activation by microtubule inhibition which decreases MSU delivery [76] ."
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"Colchicine, which inhibits tubulin polymerization and the assembly of the multimeric NLRP3 inflammasome, reduces major cardiovascular events (MACE) in patients with chronic stable coronary artery disease as well as those with recent myocardial infarction ."
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"Colchicine inhibits the activity of NLRP3 inflammasome via two aspects: inhibition of P2X7 receptor activation and the polymerization of ASC by interfering with the interaction between the pyrin domains (155)."
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"Fig. 2 summarizes purported mechanisms for colchicine inhibition of the NLRP3 Inflammasome.Considering this novel effect upon the NLRP3 inflammasome, in addition to the well-known actions on micro tub[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Also, colchicine has shown to effectively block NLRP3 inflammasome function both in animal and human studies, in addition to several other actions on inflammatory cells."
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"The anti‐inflammatory drug colchicine inhibits NLRP3 activity 10 as part of its well‐known microtubule‐disassembling properties."
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"Colchicine is known to block the NLRP3 inflammasome in vitro, however, attempts by dozens of clinical trials with low-dose colchicine to treat COVID-19 have been rather discouraging [16,17]."
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"Since colchicine inhibits the NLRP3 inflammasome, it has been postulated for use in SARS-CoV-2 infection [6]."
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"As colchicine has been shown to prevent assembly of the NLRP3 inflammasome and ameliorate other inflammatory conditions, we aimed to evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in adults with obesity and MetS."
| PMC
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"Colchicine may inhibit activation of NLRP3 inflammasome and additionally may inhibit directly the synthesis of TNF-α and IL-6 [93]."
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"In recent study, the colchicine could reduce the NLRP3 inflammasome activity or its downstream mediators in the cancer related to chronic inflammation diseases such as the hyperlipidemia with atherosclerosis, tobacco use with chronic obstructive pulmonary disease (COPD) and chronic colitis [1, 5, 11–13]."
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"Colchicine reduces left ventricular NLRP3 inflammasome activity in experimental Coxsackievirus B3-induced myocarditis."
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"Given the relevance of the cardiac NLRP3 inflammasome in CVB3 myocarditis 7 , 8 , 9 and the capacity of colchicine to reduce NLRP3 inflammasome activity, 10 we next investigated the impact of colchicine on NLRP3 inflammasome activity in cardiac immune cells."
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"For example, colchicine and canakinumab suppress upstream activation of NLRP3 inflammasome and IL-1β, therefore blocking its multifold effects on immune- and non-immune cells for transformation into p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The assembly of the NLRP3 inflammasome is driven by the spatial arrangement of the tubule network and by disrupting this network colchicine is able to inhibit the assembly and activation of the NLRP3-inflammasome complex [94,218]."
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"We show that colchicine applied in the early phase of viral infection decreases splenic NLRP3 inflammasome activity, which was associated with lower myocardial immune cell infiltration and improved LV function."
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"While the mechanisms of action of colchicine to inhibit NLRP3 inflammasome remain an area of ongoing research, colchicine has been previously shown to inhibit the activation of NLRP3 inflammasome."
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"It is worth noting that colchicine might diminish the formation of NLRP3 inflammasomes by inhibiting P2X7 receptors, exhibiting a modest inclination towards reducing hospitalization or mortality among COVID-19 patients [72]."
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